High throughput method for constructing and screening compound library and reaction device

1 . A method for constructing and screening a high-throughput compound library comprising the following steps:

(a) providing a reactor comprising n reaction chambers, wherein the reaction chambers are each independent and addressable, and the n reaction chambers constitute an addressable array of then reaction chambers;

(b) performing m independent synthesis reactions in the n reaction chambers, and obtaining a respective synthetic product in the n reaction chambers in which the synthesis reactions are carried out, thereby constructing and obtaining a compound library; wherein, each of the m independent synthesis reactions, comprises the following steps:

(b0) in an inert solvent, in the presence of a base, reacting a primary amine R—NH 2 with FSO 2 N 3 (fluorosulfonyl azide) to obtain a 1,3-dipolar cyclization reagent R—N 3 ;

wherein R is R 1 or

R1 and R2 are each independently drug active fragment, R 1 and R 2 are each independently substituted or unsubstituted groups selected from the group consisting of alkyl, cycloalkyl, heteroalkyl, heterocyclyl, alkenyl, cycloalkenyl, alkynyl, aryl, heteroaryl, sulfonyl, or a combination thereof; and

(b1) in a reaction chamber of then reaction chambers, in an inert solvent, carrying out a 1,3-dipolarcycloaddition reaction with the 1,3-dipolar cyclization reagent R—N 3 obtained in b(0) and a reaction substrate containing a terminal unsaturated bond, thereby forming a reaction product containing 1,3-dipolar ring selected from formula II, formula III or formula IV, and the 1,3-dipolarcycloaddition reaction is selected from the group consisting of:

wherein R, R′, R″ and R″′ are each independently R 1 or

 denotes a point of attachment to the terminal unsaturated bond in the reaction substrate selected from the group consisting of R′—CH═CH 2 , R′—C≡CH, or R′—C≡N; and

(c) adding to the synthetic product in each of the n reaction chambers an activity test reagent selected from the group consisting of enzymes, proteins, nucleic acids, cells, small molecule compounds, and combinations thereof, respectively, to carry out an activity test, thereby carrying out activity screening on each synthetic product; wherein, n is a positive integer ≥10, and m is a positive integer ≤n, and m≥10.

2 . The method of claim 1 , wherein each of the n reaction chambers independently has a volume of 5 microliters (μL) to 5000 μL.

3 . The method of claim 1 , wherein the activity test reagent is selected from the group consisting of an antibody, an antigen, a ligand, a ligand/receptor binding inhibitor, an angiogenesis inhibitor, a cell adhesion inhibitor, a gene expression inhibitor, an enzyme inhibitor, wherein the enzyme inhibitor is selected from the group consisting of tyrosinase inhibitor, cyclooxygenase inhibitor, telomerase inhibitor, matrix metalloprotein inhibitor, prostaglandin D synthesis inhibitor, phosphodiesterase inhibitor, cholinesterase inhibitor, viral protease inhibitor, reverse transcriptase inhibitor, and combinations thereof.

4 . The method of claim 1 , further comprising detecting, in each of the n reaction chambers, the presence or absence of a reaction product.

5 . The method of claim 1 , wherein the 1,3-dipolar cycloaddition reaction is:

wherein R and R″ are as defined in claim 1 .